Dynorphins are a family of opioid peptides derived from a single precursor and known to have a wide profile of pharmacological actions. Since the pharmakinetics vary with peptide size, the catabolism of dynorphin A (the most active kappa-selective fragment) will be emphasized to determine the nature of enzyme(s) present in different brain fractions (SPM, Golgi fractions, etc.) responsible for C-terminal shortening, and hence alteration of the address signals directed towards the different opioid receptor types. To confirm observations made in preliminary studies with brain fractions, a number of key C- terminally active enzymes will be purified and used in a coordinate manner to demonstrate production of active dynorphin intermedicates. Such enzymes will include one or more membrane bound carboxypeptidases active at pH 5-6.5, angiotension coverting enzyme, cysteine proteinases with peptidyl dipeptidase actions (cathepsin B), and prolyl endopeptidase. With the aim of developing new classes of inhibitor active in vivo, a number of known synthetic compounds will be compared to ones recently synthesized in the laboratory, or purified from brain fractions themselves. Such materials will include a new class of potent cysteine proteinase inhibitors shown to suppress conversion of prodynorphins or proenkephalins.